title: Gravity loading induces adenosine triphosphate release and phosphorylation of extracellular signal-regulated kinases in human periodontal ligament cells.
abstract: OBJECTIVE
  The periodontal ligament (PDL) receives mechanical stress (MS) from dental occlusion or orthodontic tooth movement. Mechanical stress is thought to be a trigger for remodeling of the PDL and alveolar bone, although its signaling mechanism is still unclear. So we investigated the effect of MS on adenosine triphosphate (ATP) release and extracellular signal-regulated kinases (ERK) phosphorylation in PDL cells.
  
  
  METHODS
  Mechanical stress was applied to human PDL cells as centrifugation-mediated gravity loading. Apyrase, Ca(2+)-free medium and purinergic receptor agonists and antagonists were utilized to analyze the contribution of purinergic receptors to ERK phosphorylation.
  
  
  RESULTS
  Gravity loading and ATP increased ERK phosphorylation by 5 and 2.5 times, respectively. Gravity loading induced ATP release from PDL cells by tenfold. Apyrase and suramin diminished ERK phosphorylation induced by both gravity loading and ATP. Under Ca(2+)-free conditions the phosphorylation by gravity loading was partially decreased, whereas ATP-induced phosphorylation was unaffected. Receptors P2Y4 and P2Y6 were prominently expressed in the PDL cells.
  
  
  CONCLUSIONS
  Gravity loading induced ATP release and ERK phosphorylation in PDL fibroblasts, and ATP signaling via P2Y receptors was partially involved in this phosphorylation, which in turn would enhance gene expression for the remodeling of PDL tissue during orthodontic tooth movement.
authors.affiliation: Department of Biochemistry, School of Dentistry, Health Sciences University of Hokkaido, Hokkaido, Japan; Department of Orthodontics, School of Dentistry, Health Sciences University of Hokkaido, Hokkaido, Japan.
authors.forename: Mai
authors.initials: M
authors.lastname: Ito
authors.forename: Toshiya
authors.initials: T
authors.lastname: Arakawa
authors.forename: Miki
authors.initials: M
authors.lastname: Okayama
authors.forename: Akiko
authors.initials: A
authors.lastname: Shitara
authors.forename: Itaru
authors.initials: I
authors.lastname: Mizoguchi
authors.forename: Taishin
authors.initials: T
authors.lastname: Takuma
mesh_terms: D000244:Adenosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D001081:Apyrase / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D002498:Centrifugation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000187:drug effects / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005881:Gingiva / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006112:Gravitation; D006801:Humans; D010513:Periodontal Ligament / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation; D058913:Purinergic Agonists / Q000494:pharmacology; D058914:Purinergic Antagonists / Q000494:pharmacology; D058920:Purinergic P2X Receptor Antagonists / Q000494:pharmacology; D058921:Purinergic P2Y Receptor Antagonists / Q000494:pharmacology; D018048:Receptors, Purinergic P2 / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D013314:Stress, Mechanical; D013498:Suramin / Q000494:pharmacology
chemical_list: C111914:N(6)-methyl-2'-deoxyadenosine 3',5'-diphosphate; D058913:Purinergic Agonists; D058914:Purinergic Antagonists; D058920:Purinergic P2X Receptor Antagonists; D058921:Purinergic P2Y Receptor Antagonists; D018048:Receptors, Purinergic P2; C104749:purinoceptor P2Y4; C099845:purinoceptor P2Y6; D013498:Suramin; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D048049:Extracellular Signal-Regulated MAP Kinases; D001081:Apyrase; D002118:Calcium
keywords: P2Y receptor; adenosine triphosphate release; extracellular signal-regulated kinases phosphorylation; gravity loading; periodontal ligament